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Development of Alendronate-conjugated Poly (lactic-co-glycolic acid)-Dextran Nanoparticles for Active Targeting of Cisplatin in Osteosarcoma.

Liu P, Sun L, Zhou DS, Zhang P, Wang YH, Li D, Li QH, Feng RJ - Sci Rep (2015)

Bottom Line: PLD/CDDP exhibited significant apoptosis of MG63 cancer cells compared to that of free CDDP.PLD/CDDP exhibited significantly higher G2/M phase arrest in MG63 cells than compared to free CDDP with a nearly 2-fold higher arrest in case of PLD/CDDP treated group (~60%).The superior inhibitory effect was further confirmed by a marked reduction in the number of CD31 stained tumor blood vessels and decrease in the Ki67 staining intensity for PLD/CDDP treated animal group.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, China.

ABSTRACT
In this study, we developed a novel poly (lactic-co-glycolic acid)-dextran (PLD)-based nanodelivery system to enhance the anticancer potential of cisplatin (CDDP) in osteosarcoma cells. A nanosized CDDP-loaded PLGA-DX nanoparticle (PLD/CDDP) controlled the release rate of CDDP up to 48 h. In vitro cytotoxicity assay showed a superior anticancer effect for PLD/CDDP and with an appreciable cellular uptake via endocytosis-mediated pathways. PLD/CDDP exhibited significant apoptosis of MG63 cancer cells compared to that of free CDDP. Approximately ~25% of cells were in early apoptosis phase after PLD/CDDP treatment comparing to ~15% for free CDDP after 48h incubation. Similarly, PLD/CDDP exhibited ~30% of late apoptosis cells comparing to only ~8% for free drug treatment. PLD/CDDP exhibited significantly higher G2/M phase arrest in MG63 cells than compared to free CDDP with a nearly 2-fold higher arrest in case of PLD/CDDP treated group (~60%). Importantly, PLD/CDDP exhibited a most significant anti-tumor activity with maximum tumor growth inhibition. The superior inhibitory effect was further confirmed by a marked reduction in the number of CD31 stained tumor blood vessels and decrease in the Ki67 staining intensity for PLD/CDDP treated animal group. Overall, CDDP formulations could provide a promising and most effective platform in the treatment of osteosarcoma.

No MeSH data available.


Related in: MedlinePlus

Cytotoxicity analysis of (a) blank nanoparticles (b) free CDDP and PLD/CDDP in MG63 osteosarcoma cancer cell. The cytotoxicity analysis was performed by MTT assay after 24 h incubation. Untreated cells were considered as control. (c) Cellular uptake of free CDDP and CDDP/PLD in MG63 cancer cells. (d) Confocal microscopy images demonstrating cellular internalization of PLD nanoparticles in MG63 cells. Data are expressed as standard deviation of the mean and n = 8. *p < 0.05 is the statistical difference between the cytotoxicity and cellular uptake of CDDP and CDDP/PLD treated group.
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f3: Cytotoxicity analysis of (a) blank nanoparticles (b) free CDDP and PLD/CDDP in MG63 osteosarcoma cancer cell. The cytotoxicity analysis was performed by MTT assay after 24 h incubation. Untreated cells were considered as control. (c) Cellular uptake of free CDDP and CDDP/PLD in MG63 cancer cells. (d) Confocal microscopy images demonstrating cellular internalization of PLD nanoparticles in MG63 cells. Data are expressed as standard deviation of the mean and n = 8. *p < 0.05 is the statistical difference between the cytotoxicity and cellular uptake of CDDP and CDDP/PLD treated group.

Mentions: In vitro cytotoxicity of blank NP, free CDDP, and PLD/CDDP was evaluated by means of 3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide (MTT) assay. At first, cytotoxicity of blank NP was determined by treating the cancer cells with increasing concentration of nanoparticles (Fig. 3a). Results clearly showed that blank NP has no serious effect on the viability of cancer cells. The cell viability remained more than 90% even when treated with maximum concentration of blank NP. The excellent biocompatibility of block copolymer-based nanomaterials is ideal for cancer targeting. Followed, cytotoxicity effect of free drug and drug-loaded formulations were investigated on MG-63 cancer cells (Fig. 3b). Results showed significant differences (p < 0.05) in cytotoxicity potential between free drug and PLD/CDDP. Although, both the formulations exhibited a concentration-dependent cytotoxic effect, however PLD/CDDP exhibited a superior anticancer effect than that of free CDDP. The moderate cell toxicity effect of CDDP was consistent with its high IC50 value (~3.89 μg/ml) whereas PLD/CDDP exhibited a low IC50 value of 1.26 μg/ml. The superior cytotoxicity of PLD/CDDP was mainly attributed to the sustained release of drug from the hydrophobic core of micelles to cancer cells24. These studies demonstrate the cytotoxicity effect of CDDP-loaded materials and highlight their ability to deliver drug and effectively disrupt the growth of osteosarcoma cells25.


Development of Alendronate-conjugated Poly (lactic-co-glycolic acid)-Dextran Nanoparticles for Active Targeting of Cisplatin in Osteosarcoma.

Liu P, Sun L, Zhou DS, Zhang P, Wang YH, Li D, Li QH, Feng RJ - Sci Rep (2015)

Cytotoxicity analysis of (a) blank nanoparticles (b) free CDDP and PLD/CDDP in MG63 osteosarcoma cancer cell. The cytotoxicity analysis was performed by MTT assay after 24 h incubation. Untreated cells were considered as control. (c) Cellular uptake of free CDDP and CDDP/PLD in MG63 cancer cells. (d) Confocal microscopy images demonstrating cellular internalization of PLD nanoparticles in MG63 cells. Data are expressed as standard deviation of the mean and n = 8. *p < 0.05 is the statistical difference between the cytotoxicity and cellular uptake of CDDP and CDDP/PLD treated group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4664968&req=5

f3: Cytotoxicity analysis of (a) blank nanoparticles (b) free CDDP and PLD/CDDP in MG63 osteosarcoma cancer cell. The cytotoxicity analysis was performed by MTT assay after 24 h incubation. Untreated cells were considered as control. (c) Cellular uptake of free CDDP and CDDP/PLD in MG63 cancer cells. (d) Confocal microscopy images demonstrating cellular internalization of PLD nanoparticles in MG63 cells. Data are expressed as standard deviation of the mean and n = 8. *p < 0.05 is the statistical difference between the cytotoxicity and cellular uptake of CDDP and CDDP/PLD treated group.
Mentions: In vitro cytotoxicity of blank NP, free CDDP, and PLD/CDDP was evaluated by means of 3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide (MTT) assay. At first, cytotoxicity of blank NP was determined by treating the cancer cells with increasing concentration of nanoparticles (Fig. 3a). Results clearly showed that blank NP has no serious effect on the viability of cancer cells. The cell viability remained more than 90% even when treated with maximum concentration of blank NP. The excellent biocompatibility of block copolymer-based nanomaterials is ideal for cancer targeting. Followed, cytotoxicity effect of free drug and drug-loaded formulations were investigated on MG-63 cancer cells (Fig. 3b). Results showed significant differences (p < 0.05) in cytotoxicity potential between free drug and PLD/CDDP. Although, both the formulations exhibited a concentration-dependent cytotoxic effect, however PLD/CDDP exhibited a superior anticancer effect than that of free CDDP. The moderate cell toxicity effect of CDDP was consistent with its high IC50 value (~3.89 μg/ml) whereas PLD/CDDP exhibited a low IC50 value of 1.26 μg/ml. The superior cytotoxicity of PLD/CDDP was mainly attributed to the sustained release of drug from the hydrophobic core of micelles to cancer cells24. These studies demonstrate the cytotoxicity effect of CDDP-loaded materials and highlight their ability to deliver drug and effectively disrupt the growth of osteosarcoma cells25.

Bottom Line: PLD/CDDP exhibited significant apoptosis of MG63 cancer cells compared to that of free CDDP.PLD/CDDP exhibited significantly higher G2/M phase arrest in MG63 cells than compared to free CDDP with a nearly 2-fold higher arrest in case of PLD/CDDP treated group (~60%).The superior inhibitory effect was further confirmed by a marked reduction in the number of CD31 stained tumor blood vessels and decrease in the Ki67 staining intensity for PLD/CDDP treated animal group.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, China.

ABSTRACT
In this study, we developed a novel poly (lactic-co-glycolic acid)-dextran (PLD)-based nanodelivery system to enhance the anticancer potential of cisplatin (CDDP) in osteosarcoma cells. A nanosized CDDP-loaded PLGA-DX nanoparticle (PLD/CDDP) controlled the release rate of CDDP up to 48 h. In vitro cytotoxicity assay showed a superior anticancer effect for PLD/CDDP and with an appreciable cellular uptake via endocytosis-mediated pathways. PLD/CDDP exhibited significant apoptosis of MG63 cancer cells compared to that of free CDDP. Approximately ~25% of cells were in early apoptosis phase after PLD/CDDP treatment comparing to ~15% for free CDDP after 48h incubation. Similarly, PLD/CDDP exhibited ~30% of late apoptosis cells comparing to only ~8% for free drug treatment. PLD/CDDP exhibited significantly higher G2/M phase arrest in MG63 cells than compared to free CDDP with a nearly 2-fold higher arrest in case of PLD/CDDP treated group (~60%). Importantly, PLD/CDDP exhibited a most significant anti-tumor activity with maximum tumor growth inhibition. The superior inhibitory effect was further confirmed by a marked reduction in the number of CD31 stained tumor blood vessels and decrease in the Ki67 staining intensity for PLD/CDDP treated animal group. Overall, CDDP formulations could provide a promising and most effective platform in the treatment of osteosarcoma.

No MeSH data available.


Related in: MedlinePlus